Dental plaque-related diseases, particularly gingivitis, periodontitis and caries, represent a major part of the global burden of oral diseases.
Periodontal diseases (gingivitis and periodontitis) are largely caused by specific gram-negative anaerobic bacterial infections, leading to the initial destruction of the soft connective tissue and, subsequently, to the disruption of the underlying alveolar bone and ligament supporting the teeth. The bacterial species Porphyromonas gingivalis has been implicated as a major etiologic agent in the development and progression of periodontitis. Other species also contributing to gingival inflammation are Treponema denticola, Prevotella denticola and Fusobacterium nucleatum. Based on the World Health Organization surveys, most children have signs of gingivitis, and among adults the initial stages of periodontal disease are highly prevalent. For example, in Europe, an estimated 15-35% of the adult population suffers from this multifactorial disease.
Dental caries (also known as tooth decay) is a disease wherein bacterial processes damage hard tooth structure. Steptococcus mutans is one of a few specialized organisms equipped with receptors that help for better adhesion to the surface of teeth, thus being an early coloniser of the dental surface and the most significant contributor to caries. The growth and metabolism of this pioneer species creates an acidic environment in the mouth which causes the highly mineralized tooth enamel to be vulnerable to decay.
In addition to the above, one further oral disorder is believed to affect a large proportion of the population: halitosis. Also referred to as bad breath, halitosis is caused by a number of volatile compounds which are derived from the bacterial degradation of sulphur-containing amino acids. The implicated bacteria (mostly Fusobacterium nucleatum, Porphyromonas gingivalis, Porphyromonas intermedia, and Treponema denticola) are located in stagnant areas in the oral cavity, such as the dorsal surface of tongue, periodontal pockets, and interproximal areas. This affection has a significant impact—personally and socially—on those who suffer from it, and is estimated to be the third-most-frequent reason for seeking dental aid, following tooth decay and periodontal disease.
Oral bacteria form a biofilm (dental plaque) on all hard and soft oral tissues which is considered to be the principal etiologic agent in the pathological conditions of the mouth. The accumulation of bacteria within the biofilm, facilitated by poor oral health maintenance, predisposes to allogenic shifts in the microbial community, leading to the onset of periodontal inflammation and caries formation, as well as contributing to halitosis.
Yeasts, and particularly, Candida albicans, may also be the cause of disorders in the oral cavity. The elderly are vulnerable to Candida infection provoked by chronic diseases, medication, poor oral hygiene, reduced salivary flow, or the impairment of the immune system. Even though the colonization by Candida may be asymptomatic, heavy growth usually leads to local candidiasis, with various types of mucosal lesions and symptoms.
Modifying the pathogenic potential of the microbiota within the oral cavity would be an interesting strategy in combating these disorders. On this direction, the introduction of probiotic lactobacilli to partially replace pathogenic microorganisms is a promising means for controlling oral infections. However, as compared with gastrointestinal affections, the use of probiotics for oral health applications has been scarcely studied. At present, very few commercial products containing probiotics are being marketed which incorporate such a health applications.
One of these products is Prodentis® from BioGaia. Prodentis is a chewing gum that contains a probiotic L. reuteri ATCC 55730 strain and has demonstrated to reduce gingivitis in a clinical trial (Twetman S, et al. “Short-term effect of chewing gums containing probiotic Lactobacillus— reuteri on the levels of inflammatory mediators in gingival crevicular fluid”. Acta Odontol Scand, 2009, vol. 67, p. 19-24). This same strain, L. reuteri ATCC 55730, has been reported to exert a strong antagonistic activity against cariogenic Streptococcus mutans (Caglar E, et al. “Salivary mutans streptococci and lactobacilli levels after ingestion of the probiotic bacterium Lactobacillus—reuteri ATCC 55730 by straws or tablets”. Acta Odontol Scand, 2009, vol. 64, p. 314-318). However, little is known about the impact of L. reuteri ATCC 55730 on other oral pathogens. Further, L. reuteri has been isolated from the intestine, not from the oral cavity, and it is not known whether this strain has the ability to form biofilms or otherwise colonise this environment in order to have a long-lasting effect. It has been shown that Lactobacillus sp. vary greatly in their adherent capacity to saliva-coated surfaces in a test model system mimicking oral cavity conditions (Stamatova I, et al. “In vitro evaluation of yoghurt starter lactobacilli and Lactobacillus rhamnosus GG adhesion to saliva-coated surfaces”. Oral Microbiol Immunol, 2009, vol. 24, p. 218-223).
Streptococcus salivarius K12 is another commercial probiotic intended for use in the oral cavity. S. salivarius K12 was isolated from the saliva of a healthy child and has been shown to perform in vitro antimicrobial activity against various bacterial species incriminated in the etiology of halitosis (Burton J P, et al. “Preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodor parameters”. J Appl Microbiol, 2006, vol. 100, p. 754-764). However, the beneficial effects of this strain are limited to the amelioration of halitosis symptoms.
Probiotics have therefore a potentiality to provide beneficial effects in the oral cavity, provided that suitable probiotic strains are identified. In this attempt, it is necessary to consider the putative benefits for the host, but also the safety of the strain, as well as possible adverse effects in the oral cavity. The latter acquires special relevance while contemplating the use of oral lactobacilli, since certain oral lactobacilli have been described as cariogenic due to their high acidogenic potential which favours the degradation of hard tissues, such as enamel and dentine.
Despite the advances in the field of oral probiotics, it is clear from the above that new probiotic strains are needed which, having a wide spectrum of benefits in the oral cavity, do not present adverse effects.